Wednesday, May 20, 2009

Nobel Laureate: Charles Robert Richet

 

The Nobel Prize in Physiology or Medicine 1913

"in recognition of his work on anaphylaxis"


Charles Robert Richet (1850 - 1935) won the Noble Prize in 1913 for discovering the phenomenon known as anaphylaxis. This is a condition where the administration of an antigen causes severe symptoms, even death. Richet found that anaphylactic shock occurs only after an animal had been previously immunized and even then only after some days had passed.

It appeared as though the first immunization took several days to develop but when the process was complete a second attempt at boosting immunization causes a severe reaction. Anaphylactic shock was rare, it only happens in a small percentage of cases. We are familiar with the risk when people are known to be allergic to peanuts or insect stings.

Today we know what causes the symptoms of anaphylaxis; it's due to massive release of histamines, prostaglandins, and leukotrienes from mast cells. The release of these chemicals produces rapid heartbeat, sweating, and constriction of the airways. The symptoms can be relieved, and death prevented, by rapid treatment with epinephrine.

The primary cause of most anaphyaxis is overproduction of antigen-specific immunoglobulin E (IgE) molecules on the mast cells.1 It's the IgE molecules that interact with the antigen to cause release of histamines etc. It's not known why some antigens lead to overproduction of IgE such that subsequent exposure to the same antigen cause a massive allergic reaction. (Normal antibodies are immunoglobulin G or IgG.2)

Immunology is complicated. That's why we can't cure asthma and other allergic reactions even though the phenomena have been intensely studied for more than 100 years.

Here's an excerpt from the 1913 Presentation Speech.
THEME:
Nobel Laureates
In an age in which the leading members of the medical profession tend to concentrate on innumerable experiments demonstrating the growing immunity of the organism towards poisons already resisted successfully once, you, Sir, have found that in certain cases a completely opposite result is produced. You did not restrict yourself to this isolated observation: studied in depth by you, it has become the foundation on which you have based the evidence of a reaction that is sometimes just as regular as the phenomenon of immunity. We are not concerned solely with specific prophylaxis; thanks to you, we are now aware of a specific anaphylaxis.

We do not discount the work of those who, following your lead, have observed similar phenomena, but to you goes the honour of having established the basis of a new biological reaction, anaphylaxis, and of having been the first to demonstrate it clearly. Thereby you have opened up to medical science an enormous field of study as yet unexplored. The Staff of Professors of the Caroline Institute wishes to reward you for this achievement by conferring on you the prize instituted by our compatriot Alfred Nobel for those «who have made the most important discovery in the field of physiology or medicine».

Please accept the warm congratulations of the Institute and myself, together with the wish of us all that success will continue to crown your devoted work.


1. I do not mean to imply that IgE molecules are produced by mast cells. They are not.

2. There are several different classes (isotypes) of antibodies; IgG, IgD, IgM, IgA, and IgE. The most abundance class is IgG—that's the one most often depicted in the textbooks. It's probably the type most people think about when they think about antibodies. I did not mean to imply that the other classes are not "normal."

[Photo Credit: Wikipedia]

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7 comments :

  1. Mast cells don't actually produce IgE, they have high affinity receptors for IgE molecules produced, like all other Igs, by B cells.

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  2. It is odd to assert that it is not known why some antigens lead to isotype switching to IgE. First off, it isn't just the nature of the antigen itself but also where it is localised. For instance, most allergic responses are due to low dose antigen exposure in mucosal surfaces of the eye, lungs, and so forth with fits with the understanding that IgE functions in anti-parasite defence. With regard to allergic antigens, they are always proteinaceous, sometimes proteases, and are usually low molecular weight and soluble. There is the hygiene hypothesis to explain the increasing prevalence of allergy in Western countries. In short, there is quite a bit known about allergy. If you were to point out how much is not known about allergy, that would be disingenuous because one could say the same about any branch of biology. It's like saying biochemistry is complicated, and that's why we don't have permanent solutions to metabolic diseases like diabetes. It is true but disingenuous.

    Also, what exactly is a normal antibody? IgG is the most abundant in serum, but IgA is the most abundant in mucus.

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  3. Dunbar says,

    It is odd to assert that it is not known why some antigens lead to isotype switching to IgE.

    No, it's not odd at all. I checked with three different Immunology Professors (Isenman, Gommerman, Martin) before I posted that and they all agree with my statement.

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  4. Normal antibodies are immunoglobulin G or IgG How is that IgM not "normal"? And yes, IgE is not "overproduced" on the mast cells. What about that fabled scientific accuracy, Larry? :-)

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  5. DK asks,

    And yes, IgE is not "overproduced" on the mast cells. What about that fabled scientific accuracy, Larry?

    I'm not sure I understand what you're on about.

    Is it the following sentence?

    The primary cause of most anaphyaxis is overproduction of antigen-specific immunoglobulin E (IgE) molecules on the mast cells

    Would you be happier if I have said "overproduction of IgE molecules which are bound to Fc reseptors on the surface of the mast cells?"

    Is that the problem? Is your complaint directed at the perceived implication that IgE is synthesized in the mast cells?

    How is that IgM not "normal"?

    Hmmmm ... perhaps I should have used the word "common" but you would probably have objected to that as well.

    The point I was trying to make, as I'm sure you know, is that IgE is different from the kind of antibodiea that most people think about.

    I've added a footnote to the posting.

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  6. Would you be happier if I have said "overproduction of IgE molecules which are bound to Fc reseptors on the surface of the mast cells?"

    Is that the problem? Is your complaint directed at the perceived implication that IgE is synthesized in the mast cells?


    Yep. If I didn't know much about antibodies, that's exactly how I'd read it - IgE is made by mast cells. Since many people learn from your blog (I certainly did on many subjects), I'd say making it unambiguous helps.

    perhaps I should have used the word "common" but you would probably have objected to that as well.No, I wouldn't. [Most] common is just fine. To me, if IgE is not "normal", it implies that it is abnormal, that there is something wrong with it - which is not true.

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  7. Interesting post. Nice to hear some classic immunology for a change.

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